Many illnesses or conditions require administration of a constant or sustained level of a medicament or biologically active agent to provide the most effective prophylactic or therapeutic. This may be accomplished through a multiple dosing regimen or by employing a system that releases the medicament in a sustained fashion.
Attempts to sustain medication levels include the use of biodegradable materials, such as polymeric matrices, containing the medicament. The use of these matrices, for example, in the form of microparticles or microcarriers, provides an improvement in the sustained release of medicaments by utilizing the inherent biodegradability of the polymer to control the release of the medicament and provide a more consistent, sustained level of medication and improved patient compliance.
However, these sustained release devices often exhibited high initial bursts of agent release and minimal agent release thereafter. Further, due to the high solution concentration of agent within and localized around these sustained release devices, the agent molecules have tended to aggregate thereby increasing immunogenicity in vivo and interfering with the desired release profile for the agent.
Therefore, a need exists for a means for sustaining the release of a biologically active agent in vivo without significant aggregate formation and thus with a reduced immune response to the agent over the release period of the agent.
This invention relates to a device for the sustained release in vivo of a water soluble, biologically active agent wherein said agent is susceptible to aggregation, comprising a drug delivery device and aggregation-stabilized, biologically active agent wherein the aggregation-stabilized agent is disposed within the drug delivery device.
There are many advantages to this sustained release device for a biologically active agent. These advantages include longer, more consistent in vivo blood levels of the agent, lower initial bursts of the agent, and increased therapeutic benefits by eliminating fluctuations in serum agent levels. The advantages also include better retention of biological activity of the agent and reduced immunogenicity when in vivo. The advantages further include more complete release of an agent from a sustained release device.